Sui Zhefeng, Shi Ying, Gao Zhiling, Yang Deguang, Wang Zhihao
Department of Nursing, Hulunbeier Vocational Technical College, Hulunbuir, Inner Mongolia 021000, P.R. China.
Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2017 Jun;15(6):4305-4311. doi: 10.3892/mmr.2017.6503. Epub 2017 Apr 24.
The present study aimed to investigate the distribution of T follicular helper (Tfh)-cell subsets in patients with hepatitis B virus (HBV) and determine the underlying mechanism of HBV regulation of Tfh cells. The frequency of peripheral blood Tfh subsets was analyzed using flow cytometry. The expression level of programmed cell death‑1 (PD‑1) and prostaglandin E2 (PGE2) was quantified using reverse transcription‑quantitative polymerase chain reaction and western blotting. The PGE2 level in culture supernatant was detected using enzyme‑linked immunosorbent assay. A Transwell chamber was used to co‑culture Tfh cells with HepG2 and HepG2.2.1.5. The percentage of inducible T‑cell costimulator (ICOS)+ and total Tfh cells was high at the immune activation (IA) group; however, it was reduced in the immune tolerance (IT), responders with HBsAg seroconversion (RP) and healthy control (HC) groups. The percentage of PD‑1+ Tfh cells was significantly higher in IA and IT compared with RP and HC. The ratio of PD‑1+/total Tfh cells was positively correlated with the load of HBV DNA; therefore, this ratio may act as an indicator for HBV replication. The expression level of PD‑1 in Tfh cells was higher in the HepG2.2.1.5 co‑cultured group compared with the HepG2 group, this may be due to the high PGE2 expression level in HBV‑infected HepG2.2.1.5 cells. The findings of the present study revealed an imbalanced distribution of PD‑1+ Tfh cells in patients with HBV at different immune phases. Additionally, HBV may upregulate the expression of PD‑1 in Tfh cells by promoting HepG2.2.1.5 to secret PGE2. Identifying the effect of HBV on Tfh‑cell subsets is crucial for improving immuno-based therapy for HBV.
本研究旨在探讨乙型肝炎病毒（HBV）患者中T滤泡辅助（Tfh）细胞亚群的分布，并确定HBV调节Tfh细胞的潜在机制。采用流式细胞术分析外周血Tfh亚群的频率。使用逆转录-定量聚合酶链反应和蛋白质印迹法定量程序性细胞死亡1（PD-1）和前列腺素E2（PGE2）的表达水平。使用酶联免疫吸附测定法检测培养上清液中的PGE2水平。使用Transwell小室将Tfh细胞与HepG2和HepG2.2.1.5共培养。免疫激活（IA）组中诱导性T细胞共刺激分子（ICOS）+和总Tfh细胞的百分比很高；然而，在免疫耐受（IT）组、HBsAg血清学转换应答者（RP）组和健康对照（HC）组中该百分比降低。与RP组和HC组相比，IA组和IT组中PD-1+ Tfh细胞的百分比显著更高。PD-1+/总Tfh细胞的比例与HBV DNA载量呈正相关；因此，该比例可能作为HBV复制的指标。与HepG2组相比，HepG2.2.1.5共培养组中Tfh细胞中PD-1的表达水平更高，这可能是由于HBV感染的HepG2.2.1.5细胞中PGE2表达水平较高。本研究结果揭示了不同免疫阶段HBV患者中PD-1+ Tfh细胞的分布失衡。此外，HBV可能通过促进HepG2.2.1.5分泌PGE2来上调Tfh细胞中PD-1的表达。确定HBV对Tfh细胞亚群的影响对于改善HBV的免疫治疗至关重要。
